Abstract
Ergothioneine is a potent non-toxic and very stable antioxidant which is synthesized by fungi, algae, and bacteria but not animals or higher plants. Ergothioneine has been widely used in cosmetics; dietary supplements; and medicine to treat diabetes, cancer, as well as cardiovascular, neurodegenerative, and liver diseases. Ergothioneine presents two tautomeric forms: thione, the majoritarian and more stable form (ERGO), and thiol (ERGT). Ergothioneine cannot cross cell membranes, and human cells rely on a specific transporter, OCTN1, to transport ingested ERGO to different parts of the body. Ergothioneine is very hydrophilic, and it is supposed to act at the water level but not at the membrane one. In this work, I studied the interaction of ERGO and ERGT with a complex biomembrane using molecular dynamics (MD). MD suggests that ERGO, but not ERGT, inserts spontaneously into the membrane interphase and can move from the membrane interphase to the water phase and vice versa, and no oligomerization was observed. Furthermore, ERGO, when inserted in the membrane, does not alter the hydrocarbon chain order. Therefore, ERGO (the thione form of ergothioneine), but not ERGT (the thiol form), might act at both the water and membrane interphase levels.